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一种用于非人灵长类动物心脏-胸腺整块移植的新技术。

A novel technique for heart-thymus en bloc transplantation in nonhuman primates.

作者信息

Nawalaniec James T, Landino Samantha M, O Jane M, Miller Cynthia L, Dehnadi Abbas, Hanekamp Isabel, Muoio Jayne Marie, Winter Casey, Hays Nicole, Allan James S, Madsen Joren C

机构信息

Department of Surgery, Massachusetts General Hospital, Boston, MA, USA.

Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA, USA.

出版信息

Sci Rep. 2024 Dec 30;14(1):31930. doi: 10.1038/s41598-024-83378-4.

DOI:10.1038/s41598-024-83378-4
PMID:39738516
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11686112/
Abstract

The thymus is a rich source of regulatory T cells and plays a role in self-tolerance. Therefore, transplantation of a vascularized donor thymus may facilitate the induction of tolerance in recipients of a cotransplanted heart allograft. To investigate this hypothesis, we developed a new technique to procure the heart and thymus en bloc from juvenile donors and transplant the composite allograft into thymectomized recipients. Thymic function was monitored by serial biopsy and flow cytometry of peripheral blood. Heart-thymus en bloc transplantation resulted in immediate revascularization of the heart and donor thymus with maintenance of normal thymic architecture, even in biopsies taken months after transplantation. Heart-thymus en bloc transplantation requires minimal modification to current heart procurement techniques. Here, we describe the details of the preparation, procurement, transplantation, and postoperative monitoring for this model, with the intention that this technique could be implemented by other investigators to study the effects of heart and thymus cotransplantation. This method could ultimately offer a new approach to tolerance induction in children.

摘要

胸腺是调节性T细胞的丰富来源,在自身耐受中发挥作用。因此,移植带血管的供体胸腺可能有助于在同时移植心脏同种异体移植物的受者中诱导耐受。为了研究这一假设,我们开发了一种新技术,从幼年供体中整块获取心脏和胸腺,并将复合移植物移植到胸腺切除的受者体内。通过连续活检和外周血流式细胞术监测胸腺功能。心脏-胸腺整块移植导致心脏和供体胸腺立即再血管化,并维持正常的胸腺结构,即使在移植数月后的活检中也是如此。心脏-胸腺整块移植对当前的心脏获取技术只需进行最小程度的修改。在此,我们描述了该模型的制备、获取、移植及术后监测的细节,目的是其他研究人员能够采用该技术来研究心脏和胸腺联合移植的效果。该方法最终可能为儿童耐受诱导提供一种新途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b47/11686112/01da04539a87/41598_2024_83378_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b47/11686112/31025a8a335d/41598_2024_83378_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b47/11686112/6e5dbadcb053/41598_2024_83378_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b47/11686112/38edd0d6f290/41598_2024_83378_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b47/11686112/22bdd14f5714/41598_2024_83378_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b47/11686112/0488986314db/41598_2024_83378_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b47/11686112/e29f5e5b1323/41598_2024_83378_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b47/11686112/5bf8b6cc8462/41598_2024_83378_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b47/11686112/01da04539a87/41598_2024_83378_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b47/11686112/31025a8a335d/41598_2024_83378_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b47/11686112/6e5dbadcb053/41598_2024_83378_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b47/11686112/38edd0d6f290/41598_2024_83378_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b47/11686112/22bdd14f5714/41598_2024_83378_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b47/11686112/0488986314db/41598_2024_83378_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b47/11686112/e29f5e5b1323/41598_2024_83378_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b47/11686112/5bf8b6cc8462/41598_2024_83378_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b47/11686112/01da04539a87/41598_2024_83378_Fig8_HTML.jpg

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本文引用的文献

1
A New Generation of Cell Therapies Employing Regulatory T Cells (Treg) to Induce Immune Tolerance in Pediatric Transplantation.新一代采用调节性T细胞(Treg)诱导儿科移植免疫耐受的细胞疗法。
Front Pediatr. 2022 May 11;10:862807. doi: 10.3389/fped.2022.862807. eCollection 2022.
2
Induction of donor-specific tolerance to heart transplantation: From concept to clinical translation.诱导心脏移植供体特异性耐受:从概念到临床转化。
J Thorac Cardiovasc Surg. 2023 May;165(5):1661-1666. doi: 10.1016/j.jtcvs.2021.12.048. Epub 2022 Jan 14.
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Experience with cultured thymus tissue in 105 children.
105 例患儿的胸腺组织培养经验。
J Allergy Clin Immunol. 2022 Feb;149(2):747-757. doi: 10.1016/j.jaci.2021.06.028. Epub 2021 Aug 4.
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Mixed chimerism and acceptance of kidney transplants after immunosuppressive drug withdrawal.免疫抑制药物停药后嵌合体混合和肾移植的接受。
Sci Transl Med. 2020 Jan 29;12(528). doi: 10.1126/scitranslmed.aax8863.
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Updated follow-up of a tolerance protocol in HLA-identical renal transplant pairs given donor hematopoietic stem cells.对接受供体造血干细胞的 HLA 配型相同的肾移植配对患者进行耐受性方案的更新随访。
Hum Immunol. 2018 May;79(5):277-282. doi: 10.1016/j.humimm.2018.01.010. Epub 2018 Feb 1.
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Development of B-cell memory in early childhood and the impact on antigen-specific tolerance after heart transplantation.幼儿期B细胞记忆的发展及其对心脏移植后抗原特异性耐受性的影响。
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Organ Transplant Tolerance for Children; in Sight for Some.儿童器官移植耐受性:部分已在望
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10
Chimerism, graft survival, and withdrawal of immunosuppressive drugs in HLA matched and mismatched patients after living donor kidney and hematopoietic cell transplantation.活体供肾和造血细胞移植后,HLA配型相合和不相合患者的嵌合现象、移植物存活及免疫抑制药物的停用
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